Variant chr17-75267839-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001370592.1(MIF4GD):c.255G>T(p.Gln85His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

MIF4GD
NM_001370592.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.578

Variant links:

Genes affected

MIF4GD (HGNC:24030): (MIF4G domain containing) This gene encodes a protein which interacts with the N-terminus of the stem-loop binding protein (SLBP) and the 3' end of histone mRNA. This interaction facilitates the activation of histone mRNA translation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

MIF4GD links:

MIF4GD (HGNC:):

MIF4GD links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29755646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIF4GD	NM_001370592.1 linkuse as main transcript	c.255G>T	p.Gln85His	missense_variant	4/6	ENST00000325102.13	NP_001357521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIF4GD	ENST00000325102.13 linkuse as main transcript	c.255G>T	p.Gln85His	missense_variant	4/6	2	NM_001370592.1	ENSP00000321625.8		A9UHW6-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250802

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000712

AC:

104

AN:

1461678

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.378G>T (p.Q126H) alteration is located in exon 5 (coding exon 4) of the MIF4GD gene. This alteration results from a G to T substitution at nucleotide position 378, causing the glutamine (Q) at amino acid position 126 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.11

T;T;.;.;.;.;.;T;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

.;T;T;.;T;T;T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.30

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.7

D;.;D;.;.;.;.;.;.;.

REVEL

Benign

0.076

Sift

Uncertain

0.028

D;.;D;.;.;.;.;.;.;.

Sift4G

Uncertain

0.015

D;D;D;D;D;.;D;.;.;D

Polyphen

0.24

B;B;P;.;.;.;.;.;.;.

Vest4

0.47

MutPred

0.33

Loss of MoRF binding (P = 0.1059);Loss of MoRF binding (P = 0.1059);.;.;.;.;Loss of MoRF binding (P = 0.1059);Loss of MoRF binding (P = 0.1059);.;Loss of MoRF binding (P = 0.1059);

MVP

0.20

MPC

0.66

ClinPred

0.77

GERP RS

-1.1

Varity_R

0.15

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over